Brain lipid sensing and nervous control of energy balance

Nutrient sensitive neurons (glucose and fatty acids (FA)) are present in many sites throughout the brain, including the hypothalamus and brainstem, and play a key role in the neural control of energy and glucose homeostasis. Through neuronal output, FA may modulate feeding behaviour as well as both insulin secretion and action. For example, central administration of oleate inhibits food intake and glucose production in rats. This suggests that daily variations in plasma FA concentrations might be detected by the central nervous system as a signal which contributes to the regulation of energy balance. At the cellular level, subpopulations of neurons in the ventromedial and arcuate hypothalamic nuclei are selectively either inhibited or activated by FA. Possible molecular effectors of these FA effects likely include chloride or potassium ion channels. While intracellular metabolism and activation of the ATP-sensitive K(+) channel appear to be necessary for some of the signaling effects of FA, at least half of the FA responses in ventromedial hypothalamic neurons are mediated by interaction with FAT/CD36, a FA transporter/receptor that does not require intracellular metabolism to activate downstream signaling. Thus, FA or their metabolites can modulate neuronal activity as a means of directly monitoring ongoing fuel availability by brain nutrient-sensing neurons involved in the regulation of energy and glucose homeostasis. Besides these physiological effects, FA overload or metabolic dysfunction might impair neural control of energy homeostasis and contribute to obesity and/or type 2 diabetes in predisposed subjects.